X-ray or γ-ray radiation, optical radiation, ultrasound waves and magnetic field have been used to examine and image biological tissue. X-rays or γ-rays propagate in the tissue on straight, ballistic lines, that is, their scattering is negligible. Thus, imaging is based on evaluation of the absorption levels of different tissue types. For example, in roentgenography the X-ray film contains darker and lighter spots: the denser bone that the X-rays cannot travel through, and the muscle, fat and tissue the X-rays can easily travel through. In more complicated systems, such as computerized tomography (CT), a cross-sectional picture of human organs is created by transmitting X-ray radiation through a section of the human body at different angles and by electronically detecting the variation in X-ray transmission. The detected intensity information is digitally stored in a computer that reconstructs the X-ray absorption of the tissue at a multiplicity of points located in one cross-sectional plane. Similar things can be done with different types of radiation, where radiation absorption levels of molecules within a tissue can reveal structure, or changes in concentrations of absorbing molecules, therefore showing changes in some aspect of the metabolism of the tissue.
Near infrared radiation (NIR) has been used to study biological tissues non-invasively, including oxygen metabolism in the brain, finger, or ear lobe, for example. The use of visible, NIR and infrared (IR) radiation for medical imaging may have several advantages over other forms of radiation: In the NIR or IR range the contrast factor between a tumor and a surrounding tissue is much larger than in the X-ray range. In addition, the visible to IR radiation is preferred over the X-ray radiation since it is non-ionizing and thus, generally causes fewer side effects. However, the visible or IR radiation is strongly scattered and absorbed in biological tissue, and the migration path cannot be approximated by a straight line, making inapplicable certain aspects of cross-sectional imaging techniques.
NIR spectrometry adapted to the principles of computerized tomography has been used for in vivo imaging. This technique utilizes NIR radiation in an analogous way to the use of X-ray radiation in an X-ray CT. The X-ray source is replaced by several laser diodes (or other light sources) emitting light in the NIR range. The NIR-CT uses a set of photodetectors that detect the light that had migrated in the imaged tissue. The detected data are manipulated by a computer in a manner similar to the detected X-ray data in an X-ray CT. Different NIR-CT systems have recognized the scattering aspect of the non-ionizing radiation and have modified the X-ray CT algorithms accordingly.
Together with intensive theoretical derivations and data acquisition protocols at many source-detector positions, the NIR field has been brought to the point where further development of 3D image resolution and achievement of improved signal-to-noise ratio is limited by the sensor/subject coupling in number, accuracy and reproducibility. The congestion of the subject's head, breast or limb due to a large number of optical coupling devices, particularly for in-magnet imaging of breast cancers, reaches the limit of convenience and accessibility. Furthermore, the uncontrolled contact positions of such fibers to the tissue, particularly the breast, have become one of the principal sources of irreproducibility in data acquisition. While compression, matching fluids, and probes are currently used, many problems could be solved if the test object could be viewed from afar in a non-intrusive, untethered fashion, particularly if the source position and detector acquisition could be consistently aimed or rapidly scanned over the tissue for multi-site data acquisition.
Brain tissue has been particularly studied by many burgeoning technologies, wherein MRI is truly versatile as being capable of imaging hemodynamic and metabolic signals in a unique fashion. Positron emission tomography (PET) has similar possibilities of large chemical specificity governed by the combination of lifetimes and radiation from radioactive isotopes. Other methods give highly specialized signals, for example, magnetoencephalography (MEG) and electronencephalography (EEG), which have respectively high and low resolution for neurophysiological signals. Optical tomography is somewhat more quantitative with respect to hemodynamic changes and has latent possibilities for measuring neuronal signals.
Furthermore, the propagation of near infrared light through tissue such as the brain and breast has been experimentally studied and theoretically modeled. Accurate theoretical models are based on Monte Carlo methods for statistical physics and the diffusion equation and on analytic expressions that show propagation into the gray matter of the brain in adults and especially in neonates. This propagation of light into cranial tissue has been verified by clinical measurements of the presence of X-ray CT-identified cranial hematomas at depths of about 3-4 cm. Detection of the oxygenation state and amount of hemoglobin has been the goal of tissue oximetry and quantitative results are obtained by time and frequency domain devices. However, single volume determination of optical parameters of a highly heterogeneous system such as the human brain may give only a fraction of the signal of a localized focal activation already shown to be highly localized by fMRI (functional magnetic resonance imaging).
The way optical spectroscopy has been used to quantitatively monitor and image tissue blood oxygenation and volume is by measuring absorption of oxyhemoglobin and deoxyhemoglobin in the NIR wavelength region: below 700 nm, light is strongly absorbed by hemoglobin, and above 900 nm, it is strongly absorbed by water. By making differential measurements at either side of the isosbestic point of oxyhemoglobin and deoxyhemoglobin absorbance (near 800 nm), it is possible to quantify the blood oxygenation and volume levels. Typically, these measurements are made at 750 nm and 830 nm.
Lastly, optical systems are relatively simple, safe, portable and affordable as required by today's health care industry. There are several optical examination and imaging devices that have been used for imaging functional activity of adult, full-term and pre-term neonate brain. These optical examination and imaging systems are described in U.S. Pat. Nos. 5,353,799; 5,853,370; 5,807,263, 5,820,558, which are incorporated by reference. These optical systems do not require subject immobilization (as do MRI and PET), nor do they require multisubject averaging of data. The images are acquired in less than half a minute and show two-dimensional resolution of blood changes to better than a centimeter. In these optical systems, however, light sources and light detectors are mounted directly next to the examined tissue or the light is coupled to the tissue using light guides (e.g., optical fibers). In these optical systems, however, the subject has to wear the optical coupler or probe. Furthermore, the optical probe has to provide electrical insulation to prevent electrical shock to the subject.
There is still a need for optical examination and imaging systems for examining various types of biological tissue including the brain or breast tissue, which the present invention manages to fulfill.